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Most of the rats switched over to sugared water when given the option, but the persistent minority continued to dose themselves with alcohol. This was in spite of the fact that pressing the lever to get the substance also delivered a slight electric shock to the paw.

The team observed that the alcohol-seeking animals behaved in a similar way to humans who are addicted to alcohol. The rodents were highly motivated to get alcohol, even though there were negative consequences and another reward option.

"We have to understand," explains senior study author Markus Heilig, who is a professor in clinical and experimental medicine at Linköping University in Sweden, "that a core feature of addiction is that you know it is going to harm you, potentially even kill you, and nevertheless something has gone wrong with the motivational control and you keep doing it."

Signaling problem in the amygdala

When the researchers looked inside the rats' brains, they discovered what might be disrupting the "motivational control." First, they looked for differences in gene expression in different parts of the brain. The biggest differences were in the amygdala.

They revealed that the gene that codes for a protein called GAT-3 was expressed at much lower levels in the amygdala of the rats that continued to choose alcohol compared with the rats that switched to sugared water.

GAT-3 is a "transporter" protein that helps to clear away GABA from around neurons. Studies have also revealed that rats that become addicted to alcohol seem to have altered GABA signaling.

To confirm that the GAT-3 gene was at fault, the scientists ran another experiment in which they silenced GAT-3 in the rats that had switched over to sugared water in preference to alcohol.

The effect was striking: the GAT-3 silenced rats began to behave similarly to their alcohol-seeking counterparts. When they were again given a choice between dosing themselves with alcohol or sugared water, they chose alcohol.

Human alcoholism has same brain feature

Finally, in collaboration with a team from the University of Texas at Austin, the researchers analyzed GAT-3 levels in human postmortem brain tissue. They found that GAT-3 levels were lower in tissue taken from individuals with "documented alcohol addiction."

The scientists believe that the findings will lead to improved treatments for alcohol dependence.

An investigation into the potential of using the muscular tension drug baclofen to treat alcohol dependence has shown some promising results but has not been able to explain what the mechanism of action might be.

"One of the things baclofen does is to suppress GABA release," Prof. Heilig explains, adding:

"We are currently working with a drug company to try to develop a second-generation molecule as a candidate for alcoholism medication that targets this signaling pathway."

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